Genetic mutations associated with sensitivity to neoadjuvant chemotherapy in metastatic colon cancer: A case report and review of literature

Abstract

BACKGROUND Colorectal liver metastases (CLM) occur in 15%-30% of patients with colorectal cancer (CRC). Advancements in next generation sequencing (NGS) can provide more precise prognoses for cancer patients and help guide clinical treatment. However, the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear, especially in patients with CLM. The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms (SNPs) that objectively predict sensitivity to neoadjuvant chemotherapy. CASE SUMMARY A 76-year-old male patient, who was diagnosed as stage IV colon cancer with liver metastases, was found to have APC/TP53/KRAS mutations. He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab. Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs. In addition, a critical literature review was performed based on a standardized appraisal form after selecting the articles. Ultimately, 21 eligible studies were appraised to assess the association between gene mutations and good prognosis. Mutations in KRAS, TP53, SMAD4, and APC were identified as being associated with a poor response to chemotherapy drugs, whereas mutations of CREBBP and POLD1 were associated with longer overall survival. CONCLUSION NGS can identify precise predictors of response to neoadjuvant chemotherapy, leading to improved outcomes for CRC patients.